Insulinresistenz: Bedeutung in Anästhesie und Intensivmedizin – Insulinresistenz und Proteinkatabolie bei kritisch Kranken

Zusammenfassung

Hyperglykäme Stoffwechselentgleisungen sind ein beim Intensivpatienten häufig zu beobachtendes Phänomen. Zur Hyperglykämie kommt es einerseits durch eine herabgesetzte Glukoseutilisation peripherer Gewebe trotz normaler oder erhöhter Plasmainsulinspiegel (periphere Insulinresistenz), andererseits durch die im Rahmen von Stressreaktion und/oder zentraler Insulinresistenz vermehrte hepatische Glukosebereitstellung infolge gesteigerter Glykogenolyse und Glukoneogenese. Da verschiedene Faktoren bei der intensivmedizinischen Behandlung eine Hyperglykämie bzw. eine Insulinresistenz bedingen oder aggravieren können, ist eine multifaktorielle Pathogenese wahrscheinlich. Tierexperimentelle Studien legen zudem nahe, dass bei der peripheren Insulinresistenz eine Störung bzw. Abschwächung des anabolen Insulinsignals resultiert.

Abstract

Hyperglycemia is a frequently observed phenomenon in critically ill patients, affecting numerous patients without a history of impaired glucose tolerance or diabetes. During critical illness, hyperglycemia may result from decreased peripheral glucose uptake and/or utilisation in presence of normal or elevated plasma insulin levels (peripheral insulin resistance) as well as an increase in hepatic glucose production due to augmented glycogenolysis and gluconeogenesis resulting from stress and/or central (hepatic) insulin resistance. As there are a number of factors that cause or aggravate hyperglycemia / insulin resistance during the intensive care unit (ICU) stay, a multifactorial etiology is likely. Furthermore, animal models of sepsis suggest a decrease in anabolic insulin signalling within skeletal muscle.

Schlüsselwörter:

Insulinresistenz - Proteinkatabolie - kritische Erkrankung

Keywords:

Insulin resistance - protein loss - critical illness

Kernaussagen

• Hyperglykämien betreffen einen Großteil der intensivmedizinisch behandelten Patienten.

• Die meisten der betroffenen Intensivpatienten haben keine vorbestehende Insulinsensitivitätsstörung.

• Durch Stress werden vermehrt Hormone mit blutzuckersteigernder Wirkung freigesetzt.

• Im Rahmen der zentralen Insulinresistenz kommt es trotz normaler oder erhöhter Insulinplasmaspiegel zur vermehrten hepatischen Glukoseproduktion bei Glykogenolyse und Glukoneogenese. Es resultiert eine Hyperglykämie.

• Bei der peripheren Insulinresistenz ist der Insulinplasmaspiegel normal oder erhöht. Trotzdem wird insulinabhängig weniger Glukose aufgenommen – insbesondere in der Skelettmuskulatur und im Fettgewebe. Es kommt zur Hyperglykämie.

• Durch den vermehrten Proteinabbau fallen mehr glukoneogene Substrate für die hepatische Glukoneogenese an.

• Bei der Insulinresistenz des Fettgewebes wird die Lipolyse gesteigert. Es resultiert ein vermehrter Anfall glukoneogener Substrate für die hepatische Glukoneogenese.

• Trauma, Inflammation, Sepsis, Zytokine, Immobilisierung, Bettruhe, Medikamente und andere Faktoren sind mit einer zentral bzw. peripher herabgesetzten Insulinsensitivität assoziiert.

• Im Rahmen der Insulinsignaltransduktion wird die Atrophiegenexpression gehemmt.

• Die hyperglykäme Stoffwechsellage ist einer der zentralen Risikofaktoren der ICU-acquired-Weakness.

• Die aktuelle Evidenzlage hinsichtlich Nutzen und Risiko der intensivierten Insulintherapie ist widersprüchlich.

• Der Großteil des pathophysiologischen Verständnisses hinsichtlich der akuten Insulinresistenz während der kritischen Erkrankung beruht bislang auf tierexperimentellen Daten.

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